We are studying the molecular basis of motility in eukaryotic cells, using the cellular slime mold Dictyostelium discoideum as our experimental system. We have found that Dictyostelium amoebae contain calmodulin, a protein responsible for mediating many of the regulatory effects of calcium. In higher organisms, calmodulin has been implicated in the regulation of myosin activity, cyclic nucleotide metabolism, and Ca++ transport. We propose to continue our characterization of Dictyostelium calmodulin and to examine its roles in Dictyostelium motility and development. We will determine whether calmodulin can regulate actin-myosin interaction and actin gel formation, both processes that are important in motility. We will test the effects of calmodulin on the enzymes that control cyclic AMP production and degradation, since these are key factors in Dictyostelium development. We will analyze changes in calmodulin and calmodulin-binding proteins that occur during development. Using the drug trifluoperazine, we will determine the effects of calmodulin inhibition on the motile and developmental capabilities of Dictyostelium cells, and will isolate and characterize mutants resistant to the drug. Thus we will utilize the advantages of the Dictyostelium system for a systematic study of the properties and function of this important protein.